ArticleJournal of hepatology2021
Protease inhibitor-based direct-acting antivirals are associated with increased risk of aminotransferase elevations but not hepatic dysfunction or decompensation.
Article in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Low-Barrier Fibrosis Screening in Hepatitis C Treatment: The Decompensated Cirrhosis in Hepatitis C Evaluation Questionnaire.Journal of viral hepatitis · 2026Article
- Article
- Hepatotoxicity Score: A New Method to Adjust for Use of Potentially Hepatotoxic Medications by Chronic Liver Disease Status.Pharmacoepidemiology and drug safety · 2024Article
- A Validated Algorithm to Identify Hepatic Decompensation in the Veterans Health Administration Electronic Health Record System.Pharmacoepidemiology and drug safety · 2024Article
- Direct-Acting Antiviral Therapy for Patients with Chronic Hepatitis C Infection and Decompensated Cirrhosis.Digestive diseases and sciences · 2024Review
- Real-world treatment outcome with protease inhibitor direct-acting antiviral in advanced hepatitis C cirrhosis: a REAL-C study.Hepatology international · 2023Article
- Safety analysis of glecaprevir/pibrentasvir in patients with markers of advanced liver disease in clinical and real-world cohorts.Journal of viral hepatitis · 2022Article
- Direct-Acting Antivirals for HCV Treatment in Decompensated Liver Cirrhosis Patients: A Systematic Review and Meta-Analysis.Journal of personalized medicine · 2022Review
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15 authors at 7 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsCases of acute liver injury (ALI) have been reported among chronic HCV-infected patients receiving protease inhibitor (PI)-based direct-acting antiviral (DAA) regimens, but no analyses have compared the risk of ALI in patients receiving PI- vs. non-PI-based DAAs. Thus, we compared the risk of 3 ALI outcomes between patients (by baseline Fibrosis-4 [FIB-4] group) receiving PI-based or non-PI-based DAAs.
methodsWe conducted a cohort study of 18,498 patients receiving PI-based DAA therapy (paritaprevir/ritonavir/ombitasvir±dasabuvir, elbasvir/grazoprevir, glecaprevir/pibrentasvir) matched 1:1 on propensity score to those receiving non-PI-based DAAs (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir) in the 1945-1965 Veterans Birth Cohort (2014-2019). During exposure to DAA therapy, we determined development of: i) alanine aminotransferase (ALT) >200 U/L, ii) severe hepatic dysfunction (coagulopathy with hyperbilirubinemia), and iii) hepatic decompensation. We used Cox regression to determine hazard ratios (HRs) with 95% CIs for each ALI outcome within groups defined by baseline FIB-4 (≤3.25; >3.25).
resultsAmong patients with baseline FIB-4 ≤3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR 3.98; 95% CI 2.37-6.68), but not severe hepatic dysfunction (HR 0.67; 95% CI 0.19-2.39) or hepatic decompensation (HR 1.01; 95% CI 0.29-3.49), compared to those receiving non-PI-based regimens. For those with baseline FIB-4 >3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR, 2.15; 95% CI 1.09-4.26), but not severe hepatic dysfunction (HR, 1.23 [0.64-2.38]) or hepatic decompensation (HR, 0.87; 95% CI 0.41-1.87), compared to those receiving non-PI-based regimens
conclusionWhile risk of incident ALT elevations was increased in those receiving PI-based DAAs in both FIB-4 groups, the risk of severe hepatic dysfunction and hepatic decompensation did not differ between patients receiving PI- or non-PI-based DAAs in either FIB-4 group. LAY SUMMARY: Cases of liver injury have been reported among patients treated with protease inhibitor-based direct-acting antivirals for hepatitis C infection, but it is not clear if the risk of liver injury among people starting these drugs is increased compared to those starting non-protease inhibitor-based therapy. In this study, patients receiving protease inhibitor-based treatment had a higher risk of liver inflammation than those receiving a non-protease inhibitor-based treatment, regardless of the presence of pre-treatment advanced liver fibrosis/cirrhosis. However, the risk of severe liver dysfunction and decompensation were not higher for patients treated with protease inhibitor-based regimens.
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